by Frederike Buhse, Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen
A research team from the Research Center Borstel, Leibniz Lung Center (FZB), Kiel University (CAU), the University of Lübeck (UzL), and the University Medical Center Schleswig-Holstein (UKSH), together with additional partners, has gained new insights into the development of post-COVID syndrome.
Using state-of-the-art single-cell transcriptomics (scRNA-seq) combined with cell biology models, the scientists were able to decipher the cellular and molecular mechanisms underlying the prolonged symptoms experienced by many affected individuals.
The study identified two messenger substances that cause persistent inflammation in the nasal mucosa. This inflammatory process appears to inhibit tissue regeneration and thus contributes to the ongoing symptoms of post-COVID syndrome.
The findings have been published in Nature Communications.
Post-COVID syndrome (PCS) affects approximately 3–17% of individuals following infection with the SARS-CoV-2 coronavirus. Those affected suffer from late or long-term effects with a wide range of symptoms, the causes of which remain largely unclear.
The team led by Dr. Karosham Reddy and Professor Markus Weckmann (both FZB), Professor Hauke Busch, and Associate Professor Dr. Anke Fähnrich from the Medical Systems Biology group at the Lübeck Institute of Experimental Dermatology (LIED), examined nasal biopsy samples from 25 patients with post-COVID syndrome at the cellular and molecular levels. The samples were collected as part of NAPKON, a nationwide post-COVID cohort.
The researchers analyzed, among other things, the existing cell types and the signaling pathways through which the cells communicate. They discovered that the mucosa of the upper respiratory tract remains structurally altered even months after recovery from a SARS-CoV-2 infection—despite the absence of an active viral infection.
In this context, they identified two key messenger substances: TNF? and TGF?. These appear to be responsible for a persistent misprogramming of the mucosal cells. Dr. Reddy and Professor Markus Weckmann at FZB were able to confirm these findings in innovative human mucosal models.
“Our data show that the combination of the two messenger substances, TNF? and TGF?, severely disrupts the regeneration of the ciliated epithelium,” explains Dr. Reddy.
“The persistent inflammation in the nasal mucosa is therefore not maintained by the virus itself, but driven by these messengers,” Reddy continues.
As a result, the airway mucosa can no longer maintain its protective function, which may lead to prolonged respiratory symptoms and increased susceptibility to infections, both typical features of PCS.
The results of the study may provide new approaches for targeted treatment of post-COVID syndrome.
“Our observations point to specific signaling pathways that appear to play a key role in PCS. These could be therapeutically targeted to alleviate symptoms and possibly prevent long-term damage to the nasal mucosa,” says lead author PD Dr. Fähnrich.
The mechanisms observed could also play a role in other chronic lung diseases, which will need to be explored in future studies.
More information:
K. D. Reddy et al, scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNF? and TGF? in post-COVID syndrome, Nature Communications (2025). DOI: 10.1038/s41467-025-64778-0
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